title: Solid dispersion prepared by continuous cogrinding in an air jet mill.
abstract: Embedding a poorly water-soluble drug as a solid dispersion in a hydrophilic carrier by cogrinding is a possible strategy for enhancing the drug dissolution rate. Although general interest in continuous processes for manufacturing drug formulations has increased, many publications still focus on batch processes. The jet mill used in this study is a promising tool for continuous cogrinding. Investigation of different drug-to-carrier ratios (griseofulvin/mannitol) demonstrated that a drug load of 10% is best suited to investigate the enhanced dissolution behavior. To gain deeper insight into the underlying mechanisms, the coground dispersion is compared with different physical mixtures in terms of physicochemical properties and dissolution behavior. Differential scanning calorimetry and X-ray powder diffraction were used to verify the crystalline structure of the coground formulation. On the basis of the Hixson-Crowell model, particle size reduction was ruled out as the main reason for dissolution enhancement. An increase of surface free energies because of grinding is shown with contact angle measurements. Confocal Raman microscopy investigations revealed the drug's bulk dispersity in the coground formulation as an additional factor for the increased dissolution rate. In conclusion, the continuous cogrinding approach is a promising technique to prepare the drug in a rapidly dissolving, yet crystalline, form.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, 40225, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Muehlenfeld
authors.forename: Birthe
authors.initials: B
authors.lastname: Kann
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
authors.forename: Markus
authors.initials: M
authors.lastname: Thommes
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D006118:Griseofulvin / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry*; D010316:Particle Size; D033362:Powder Diffraction; D012995:Solubility; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D006118:Griseofulvin; D008353:Mannitol
keywords: Raman spectroscopy; X-ray powder diffractometry; calorimetry (DSC); dissolution rate; milling; physicochemical properties; poorly water-soluble drugs; solid dispersion; surface energy; wetting and contact angle